Celecoxib is a non-steroidal anti-inflammatory drug (NSAID) that has anti-inflammatory, analgesic, and antipyretic properties. The mechanism of action of celecoxib is believed to be due to inhibition of prostaglandin synthesis, primarily via inhibition of cyclooxygenase-2 (COX-2).
Celecoxib is indicated for the relief of signs and symptoms associated with osteoarthritis, rheumatoid arthritis, acute pain, primary dysmenorrhea, as well as the reduction of the number of adenomatous colorectal polyps in familial adenomatous polyposis as an adjunct to usual care (e.g., endoscopic surveillance, surgery). While celecoxib has been known to be effective in the treatment of the aforementioned diseases, it may also lead to adverse events including severe cardiovascular adverse reactions. Hence, celecoxib dosage forms require an FDA boxed warning on their labeling which warns physicians that this drug may cause myocardial infarctions and other cardiovascular complications, such as hypertension. It has also been established that celecoxib raises blood pressure and negates the effects of most anti-hypertensive drugs. Indeed, the labeling document for celecoxib warns that it may lead to hypertension, and that patients taking antihypertensives such as thiazides and diuretics may have an impaired response to these therapies.
U.S. Pat. No. 9,408,837 describes a method for ameliorating celecoxib-induced elevation of blood pressure in a subject. The method comprises a) administering at least one dose of celecoxib, wherein the at least one dose of celecoxib is sufficient to cause elevation in blood pressure in the subject; and b) administering at least one dose of amlodipine at a dosage which is sufficient to ameliorate blood pressure elevation in the subject.
US 2016/0058744 describes an oral dosage composition comprising: amlodipine or a pharmaceutically acceptable salt thereof; and celecoxib or a pharmaceutically acceptable salt thereof, wherein said amlodipine and celecoxib or pharmaceutically acceptable salts thereof are present together in a single dosage form.
There is an unmet need for single dosage forms of celecoxib and amlodipine or pharmaceutically acceptable salts thereof which are stable during manufacturing and storage.